Combined treatment with corticosteroids and moclobemide favors normalization of hypothalamo-pituitary-adrenal axis dysregulation in relapsing-remitting multiple sclerosis: A randomized, double blind trial

Hyperresponsiveness of the hypothalamo-pituitary-adrenal (HPA) axis in mult iple sclerosis (MS), an autoimmune inflammatory disease of the central nerv ous system, is presumably due to diminished corticosteroid receptor functio n. It probably influences the immune response, but its clinical significanc e is not clear. Similar HPA dysregulation occurs in depression and is rever sible with successful antidepressant treatment. We conducted a double blind , placebo-controlled trial to evaluate the neuroendocrine effect of cotreat ment with the antidepressant moclobemide as an adjunct to oral corticostero ids in MS. Twenty-one patients with definite relapsing-remitting MS (11 females, aged 33.9 +/- 2.0 yr; Expanded Disability Status Scale score of neurological imp airment. 2.0-6.5) in acute relapse were treated with placebo (n = 13) or 30 0 mg moclobemide (reversible monoamine oxidase A inhibitor; n = 8) for 75 d ays. All received oral fluocortolone from day 7 on, and the dose was tapere d until day 29. Effects were evaluated using the combined dexamethasone-CRH test and clinically on days 1, 30, and 75. At baseline, the HPA axis was mildly activated, comparably for treatment groups [area under the curve for cortisol (AUC-Cort), 213.8 +/- 76.8 arbitrary units in the mo clobemide group us. 225.8 +/- 65.1 in the steroid alone group; mean +/- SEM ]. In a group of healthy controls with comparable demographic characteristi cs, the AUC-Cort was 107.4 +/- 14.1. Moclobemide cotreatment resulted in no rmalization of the HPA axis response, whereas the HPA system hyperresponse was maintained with steroids alone (AUC-Cort on day 30, 85.9 +/- 22.8 us. 1 77.1 +/- 68.5; on day 75, 111.0 +/- 46.0 us. 199.2 +/- 64.6). The change in Expanded Disability Status Scale was comparable for both groups. Although corticosteroids alone had no effect on the HPA response using the dexamethasone-CRH test, treatment with moclobemide combined with corticoste roids favors normalization of the HPA response in relapsing-remitting MS.